Advair Safety and Black Box Warning

Safety of Advair, side effects, and cautions

advair diskus with black box warning
What does Advair have a black box warning, and is it safe to use for asthma and COPD?. Daniel More, MD

If your doctor has recommended Advair, you may feel panicked to learn that it has a black box warning. What exactly is a black box warning? What are the potential side effects and safety issues associated with the use of Advair? And how can you weigh the risks and benefits not just of Advair, but all medical treatments you consider?

What is Advair?

Advair (fluticasone/salmeterol) is an inhaled medication used to treat asthma and chronic obstructive pulmonary diseases (COPD) such as emphysema, chronic bronchitis, and bronchiectasis.

It is a combination medication consisting of an inhaled steroid and a long-acting form of the beta agonist medication albuterol, called Serevent (salmeterol). The combination of these medications works especially well to control the inflammation in asthma. The salmeterol does not replace the need for rescue inhalers, such as albuterol, which are still needed for the immediate relief of asthma symptoms, and, in fact, should be avoided when a rescue medication is needed.

Medications included in the black box warning include Advair Diskus, Foradil Aerolizer, and Serevent diskus.

What is a Black Box Warning?

A black box warning is a precautionary statement given by the Food and Drug Administration informing the public that a medication may cause a serious or life threatening adverse reaction.

The term "black box" refers to the box on packaging information in which the warning is issued. Black box warnings have been issued for medications for many years, but have become much more common over the past few decades.

A black box warning may be granted for several reasons ranging from the ability of the drug to cause conditions ranging from birth defects to tendon rupture to suicidal thoughts. In other words, a black box warning indicates that there is potentially a problem with a drug, but does not state exactly what that problem may be.

Many manufacturers enclose guides along with these medications explaining the black box warning in greater depth.

You may be wondering why a black box warning is sometimes only added long after a medication has been approved by the FDA. The reason is that clinical trials look at potential safety issues, but some of those issues are not found until the drug is used widely among the public.

Understanding the Black Box Warning with Advair

The black box warning for Advair was listed in 2003. This warning came about as a result of various studies on the safety of salmeterol, the bronchodilator portion of the medications.

The largest study, called the SMART trial, showed a small increase in the risk of death and hospitalization asthma and breathing problems when taking salmeterol, particularly in African-American patients. For this reason, the FDA placed a “black box” warning on salmeterol, as well as Foradil (formoterol), which works in much the same way.

The SMART trial did not study Advair, but since Advair contains salmeterol, the “black box” warning was also given to this medication. In fact, any medication that contains salmeterol or formoterol also has the same “black box” warning.

Salmeterol and formoterol are long-acting beta agonist (LABA).

used in the treatment of moderate and severe asthma. LABAs are not an adequate controller therapy by themselves for asthma, and can potentially cause life-threatening asthma attacks if used alone. This fact has been known for years, just as it is well-known that overuse of albuterol, or any other rescue medication, can place a person at risk for severe asthma attacks, and even death from asthma. A person with asthma, therefore, should always use an inhaled steroid for treatment of their asthma when a LABA is required.

Unfortunately, the SMART trial did not address whether a particular patient was taking an inhaled steroid for their asthma, only if salmeterol was safe by itself in the treatment of asthma.

Most of the patients with the most severe asthma, particularly African-American patients, were not taking an inhaled steroid when placed on the LABA. However, when the study went back and looked at the patients who were taking an inhaled steroid along with the LABA, there did not appear to be an added risk of severe asthma attacks or death from asthma, even in the African-American patients.

Further testing to get to the bottom of the remaining questions was started in 2011 and is expected to be completed in 2011.

Should I Take Advair if I Have Asthma?

The FDA states that a LABA medication should not be used if a person with asthma is controlled on an inhaled steroid alone, and should never be the first medication which is prescribed for asthma.

If asthma is not controlled on an inhaled steroid, or the level of asthma is classified as being moderate to severe, then combination therapy including an inhaled steroid and a LABA can be a good choice of therapy. Other treatment choices include increasing the dose of the inhaled steroid or the addition of another medication such as Singulair (montelukast) or theophylline. These other medication choices may not control asthma as well as the combination of an inhaled steroid and LABA.

For most people with moderate to severe asthma, or those whose asthma is not controlled on an inhaled steroid alone, the benefits of a LABA medication outweigh the risks. However, it is important for a person to know the risks and benefits of taking any medication, particularly those with a “black box” warning. Learn more about the treatment options available for asthma.

Long Acting Beta Agonists in Children

As with adults, we are awaiting further studies looking at the safety of LABA drugs in children. A 2015 review of studies to date found that the additions of long-acting beta-agonists to inhaled steroids did not result in a reduced rate of asthma exacerbations or the need for oral steroid medications. They did, however, improve lung function. If your child's allergist is considering adding a LABA drug, talk to her about what you may expect to gain and what the risks are in children in particular.

Bottom Line - Weighing the Risks and Benefits of Medical Treatments

It's important to realize that nearly every medical treatment available, whether a drug or a procedure, can have side effects and result in adverse events. In some ways, weighing the risks and benefits of Advair is easier as a warning is included and both patients and physicians are well aware of this potential problem.

If you are considering using Advair, have a good talk with your oncologist. Make sure you have considered any other possible options, including avoiding the conditions which trigger your asthma. Make sure to go over the risk factors for asthma as well. Many of these are out of your control, but others may be easily remedied. For example, a low vitamin D level is a risk factor for asthma attacks and a simple blood test can determine if your levels are too low. Avoid secondhand smoke. Learn about and get treated for GERD if that is a factor in your asthma.

Make sure that you have an asthma action plan in place, and never hesitate to call your doctor or to go to the emergency if you think you may be in trouble.


Cates, C., Wieland, L., Oleszczuk, M., and K. Kew. Safety of Regular Formoterol or Salmeterol in Adults with Asthma: An Overview of Cochrane Reviews. Cochrane Database of Systematic Reviews. 2014. (2):CD010314.

Chauhan, B., Chartrand, C., Ni Chroinin, M., Milan, S., and F. Ducharme. Addition of Long-Acting Beta2-Agonists to Inhaled Corticosteroids for Chronic Asthma in Children. Cochrane Database of Systematic Reviews. 2015. (11):CD007949.

Sears, M. Safety of Long-Acting Beta-Agonists: Are New Data Really Required?. Chest. 2009. 136(2):604-7.

U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA requires post-market safety trials for Long-Acting Beta-Agonists (LABAs). 04/15/11.

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